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• W2509356670 startingPage "5049" @default.
• W2509356670 abstract "A key pathogenic agent in Alzheimer's disease (AD) is the amyloid β-protein (Aβ), which self-assembles into a variety of neurotoxic structures. Establishing structure-activity relationships for these assemblies, which is critical for proper therapeutic target identification and design, requires aggregation and neurotoxicity experiments that are properly controlled with respect to the Aβ peptide itself. Reverse Aβ or non-Aβ peptides suffer from the fact that their biophysical properties are too similar or dissimilar, respectively, to those of native Aβ for them to be appropriate controls. For this reason, we used simple protein design principles to create scrambled Aβ peptides predicted to behave distinctly from native Aβ. We showed that our prediction was true by monitoring secondary structure dynamics with thioflavin T fluorescence and circular dichroism spectroscopy, determining oligomer size distributions, and assaying neurotoxic activity. We then demonstrated the utility of the scrambled Aβ peptides by using them to control experiments examining the effects of Aβ monomers, dimers, higher-order oligomers, and fibrils on gene expression in primary rat hippocampal neurons. Significant changes in gene expression were observed for all peptide assemblies, but fibrils induced the largest changes. Weighted gene co-expression network analysis revealed two predominant gene modules related to Aβ treatment. Many genes within these modules were associated with inflammatory signaling pathways." @default.
• W2509356670 created "2016-09-16" @default.
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• W2509356670 date "2016-08-29" @default.
• W2509356670 modified "2023-10-03" @default.
• W2509356670 title "Design, Characterization, and Use of a Novel Amyloid β-Protein Control for Assembly, Neurotoxicity, and Gene Expression Studies" @default.
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• W2509356670 doi "https://doi.org/10.1021/acs.biochem.6b00579" @default.
• W2509356670 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27505174" @default.
• W2509356670 hasPublicationYear "2016" @default.
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